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目的:探讨基质金属蛋白酶2(MMP-2)反义寡核苷酸对人膀胱癌裸鼠异体移植瘤生长的抑制作用。方法:制备膀胱癌裸鼠移植瘤模型18只,随机分为3组:MMP-2反义寡核苷酸(ASODN)治疗组、MMP-2正义寡核苷酸(SODN)治疗组及对照组,每组6只。待瘤结节直径≥5 mm后,分别在肿瘤细胞接种部位周围及中心皮下注射反义寡核苷酸/阳离子脂质体复合物、正义寡核苷酸/阳离子脂质体复合物和生理盐水。每周2次,连续4周,断颈处死裸鼠,计算肿瘤体积,称量瘤重。常规切片,HE染色,观察组织学形态并进行病理学评估。应用免疫组织化学技术(SP法)检测各组移植瘤组织中PCNA蛋白表达。结果:与对照组瘤重(7.49±0.53)g比较,ASODN组瘤重(4.18±0.53)g明显降低(P<0.01);ASODN组、正义寡核苷酸(SODN)组抑瘤率分别为44.19%、8.41%(P<0.01);ASODN组、对照组增殖指数(P1值)分别为27.63%、88.39%,抑制率为60.76%(P<0.01);ASODN组瘤体病理学特征改善。结论:MMP-2反义寡核苷酸能抑制裸鼠体内移植瘤生长,通过反义寡核苷酸下调MMP-2的表达,降低癌细胞的增殖活性,有效逆转肿瘤的恶性表型,为膀胱癌的基因治疗提供了实验依据。
Objective: To investigate the inhibitory effect of matrix metalloproteinase 2 (MMP-2) antisense oligonucleotide on the growth of human bladder cancer xenograft in nude mice. Methods: Eighteen bladder cancer xenografts in nude mice were randomly divided into 3 groups: ASODN-treated group, MMP-2-positive control group and control group , 6 in each group. After tumor nodules were> 5mm in diameter, antisense oligonucleotide / cationic liposome complexes, antisense oligonucleotide / cationic liposome complex and saline were injected subcutaneously around and in the tumor cell inoculation sites, respectively . Twice a week for 4 weeks, the nude mice were sacrificed and the tumor volume was calculated and weighed. Routine sections, HE staining, histological observation and pathological evaluation. The expression of PCNA in each group was detected by immunohistochemistry (SP method). Results: The tumor weight (4.18 ± 0.53) g in ASODN group was significantly lower than that in control group (7.49 ± 0.53) g (P <0.01). The inhibition rates of ASODN group and SODN group were 44.19%, 8.41% (P <0.01). The proliferation index (P1) of ASODN group and control group were 27.63% and 88.39% respectively, the inhibition rate was 60.76% (P <0.01). The pathological features of ASODN group were improved. CONCLUSION: Antisense oligonucleotides of MMP-2 can inhibit the growth of xenografts in nude mice and down-regulate the expression of MMP-2 by antisense oligodeoxynucleotides to reduce the proliferative activity of cancer cells and effectively reverse the malignant phenotype of tumors Gene therapy of bladder cancer provides experimental evidence.